3D Microphysiological System-Inspired Scalable Vascularized Tissue Constructs for Regenerative Medicine

Abstract

Microphysiological systems (MPSs), based on microfabrication technologies and cell culture, can faithfully recapitulate the complex physiology of various tissues. However, 3D tissues formed using MPS have limitations in size and accessibility; their use in regenerative medicine is, therefore, still challenging. Here, an MPS-inspired scale-up vascularized engineered tissue construct that can be used in regenerative medicine is designed. Endothelial cell-laden hydrogels are sandwiched between two through-hole membranes. The microhole array in the through-hole membranes enables the molecular transport across the hydrogel layer, allowing long-term cell culture. Furthermore, the time-controlled delamination of through-hole membranes enables the harvesting of cell-cultured hydrogel constructs without damaging the capillary network. Importantly, when the tissue constructs are implanted in a mouse ischemic model, they protect against necrosis and promoted functional recovery to a greater extent than implanted cells, hydrogels, and simple gel-cell mixtures.